It is proposed to determine the high resolution X-ray crystal structure of the enzyme yeast pyrophosphatase. This enzyme crystallizes in the space group P21 with one molecule of molecular weight 71,000 in the asymmetric unit of the unit cell. Diffraction data will be recorded on films and measured by a scanning microdensitometer. The phases of the reflections will be determined by the method of isomorphous replacement using mercurials and lanthanide ions, among others, as the replacing heavy atoms. The three-dimensional structure of the enzyme will be elucidated from consideration of the resulting electron density map and the amino acid sequence of the protein. The mode of substrate binding and any changes in protein conformation on binding the substrate will be determined from structural studies of enzyme- inhibitor complexes. This structural information, when taken together with chemical and kinetic data, should lead to the elucidation of the catalytic mechanism of the enzyme. Such a mechanism could quite possibly be developed into a general model of biological phosphate transfer reactions.